Drug Interaction Report

MONITOR: The use of omacetaxine with other immunosuppressive or myelosuppressive agents may increase the risk of infections. Omacetaxine alone may cause severe myelosuppression, neutropenia, lymphopenia, and opportunistic infections. In clinical trials, infections/infestations (bacterial, viral, fungal, and nonspecified) were reported in up to 56% of patients, and grade 3 or 4 infections/infestations in up to 20% of patients. The risk may theoretically increase when coadministered with other hematotoxic therapy. Agents that may be significantly myelo- or immunosuppressive include antineoplastic agents, radiation, zidovudine, linezolid, some antirheumatic agents, high dosages of corticosteroids or adrenocorticotropic agents (greater than 10 mg/day to 1 mg/kg/day, whichever is less, of prednisone or equivalent for more than 2 weeks), and long-term topical or inhaled corticosteroids.

MANAGEMENT: Caution is advised if omacetaxine must be used in patients who have recently received or are receiving treatment with other immunosuppressive or myelosuppressive drugs, and vice versa. Close clinical and laboratory monitoring for the development of severe hematologic adverse effects is recommended both during and after discontinuation of therapy. Patients should be advised to seek medical attention if they experience symptoms such as fever, chills, shortness of breath, fatigue, and any unusual bleeding or bruising.

Coadministration with grapefruit juice may increase the bioavailability of oral estrogens. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall induced by certain compounds present in grapefruits. In a small, randomized, crossover study, the administration of ethinyl estradiol with grapefruit juice (compared to herbal tea) increased peak plasma drug concentration (Cmax) by 37% and area under the concentration-time curve (AUC) by 28%. Based on these findings, grapefruit juice is unlikely to affect the overall safety profile of ethinyl estradiol. However, as with other drug interactions involving grapefruit juice, the pharmacokinetic alterations are subject to a high degree of interpatient variability. Also, the effect on other estrogens has not been studied.